The epidemiological association of both chronic alcohol and tobacco consumption with cancers of the head and neck area has been well documented. Our woking hypothesis assumes that tobacco, and/or tobacco smoke, is the source of the initiating carcinogenic stimuli and that ethanol facilitates the metabolic activation of tobacco-associated carcinogens. Our previous studies have shown that chronic ethanol consumption by Syrian golden hamsters enhances liver microsomal Alpha-hydroxylation of the tobacco-associated carcinogens N-nitrosopyrrolidine (NPYR), N'-nitrosonornicotine (NNN), and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), as well as the mutagenicity and carcinogenicity of NPYR. The proposed series of investigations are designed to determine: (1) the effect of alcohol consumption on the metabolism of tobacco-associated carcinogens by target tissues--trachea (NNN, NPYR, and B(a)P), lung (B(a)P), and oral cavity (NPYR and B(a)P); (2) the critical time of ethanol consumption for expression of enhanced carcinogenicity of NPYR; (3) the effect of liver damage on the metabolism of NPYR, NNN, and B(a)P; and (4) the effect of liver damage on the carcinogenicity of NPYR.